"The U.S. Food and Drug Administration yesterday approved Obizur [Antihemophilic Factor (Recombinant), Porcine Sequence] for the treatment of bleeding episodes in adults with acquired hemophilia A (acquired Factor VIII [FVII] deficiency).
Percutaneous Coronary Intervention
DOSAGE AND ADMINISTRATION
Each 250 mL polyolefin bag contains 250 mg of argatroban (1 mg/mL); and, as supplied, is ready for intravenous infusion. Dilution is not required.
Argatroban Injection is a clear, colorless to pale yellow solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use if the solution is cloudy, contains precipitates, or if the flip-off seal is not intact.
Dosing In Patients With Heparin-Induced Thrombocytopenia
Before administering Argatroban Injection, discontinue heparin therapy and obtain a baseline aPTT. The recommended initial dose of Argatroban Injection for adult patients without hepatic impairment is 2 mcg/kg/min, administered as a continuous infusion (see Table 1).
Table 1: Recommended Doses and Infusion Rates for 2
mcg/kg/min Dose of Argatroban Injection for Patients With HITa and
Without Hepatic Impairment (1 mg/mL Concentration)
|Body Weight (kg)||Dose (mcg/min)||Infusion Rate (mL/hr)|
|awith or without thrombosis|
For use in HIT, therapy with Argatroban Injection is monitored using the aPTT with a target range of 1.5 to 3 times the initial baseline value (not to exceed 100 seconds). Tests of anticoagulant effects (including the aPTT) typically attain steady-state levels within 1 to 3 hours following initiation of Argatroban Injection. Check the aPTT 2 hours after initiation of therapy and after any dose change to confirm that the patient has attained the desired therapeutic range.
After the initiation of Argatroban Injection, adjust the dose (not to exceed 10 mcg/kg/min) as necessary to obtain a steady-state aPTT in the target range [see Clinical Studies].
Dosing In Patients Undergoing Percutaneous Coronary Intervention
Initiate an infusion of Argatroban Injection at 25 mcg/kg/min and administer a bolus of 350 mcg/kg via a large bore intravenous line over 3 to 5 minutes (see Table 2). Check an activated clotting time (ACT) 5 to 10 minutes after the bolus dose is completed. The PCI procedure may proceed if the ACT is greater than 300 seconds.
If the ACT is less than 300 seconds, an additional intravenous bolus dose of 150 mcg/kg should be administered, the infusion dose increased to 30 mcg/kg/min, and the ACT checked 5 to 10 minutes later (see Table 2).
If the ACT is greater than 450 seconds, decrease the infusion rate to 15 mcg/kg/min, and check the ACT 5 to 10 minutes later (Table 3).
Continue titrating the dose until a therapeutic ACT (between 300 and 450 seconds) has been achieved; continue the same infusion rate for the duration of the PCI procedure.
In case of dissection, impending abrupt closure, thrombus formation during the procedure, or inability to achieve or maintain an ACT over 300 seconds, additional bolus doses of 150 mcg/kg may be administered and the infusion dose increased to 40 mcg/kg/min. Check the ACT after each additional bolus or change in the rate of infusion.
Table 2: Recommended Starting and Maintenance Doses
(Within the Target ACT Range) of Argatroban Injection in Patients Undergoing
PCI Without Hepatic Impairment (1 mg/mL Concentration)
|Body Weight (kg)||Starting Bolus Dose (350 mcg/kg)||Starting and Maintenance Continuous Infusion Dosing For ACT 300 to 450 seconds 25 mcg/kg/min|
|Bolus Dose (mcg)||Bolus Volume (mL)||Continuous Infusion Dose (mg/min)||Continuous Infusion Rate (mL/hr)|
|NOTE: 1 mg = 1000 mcg; 1 kg = 2.2 lbs|
Table 3: Recommended Dose Adjustments of Argatroban
Injection for Patients Outside of ACT Target Range Undergoing PCI Without
Hepatic Impairment (1 mg/mL Concentration)
|Body Weight (kg)||If ACT Less than 300 seconds Dosage Adjustment† 30 mcg/kg/min||If ACT Greater than 450 seconds Dosage Adjustment* 15 mcg/kg/min|
|Additional Bolus Dose (mcg)||Bolus Volume (mL)||Continuous Infusion Dose (mcg/min)||Continuous Infusion Rate (mL/hr)||Continuous Infusion Dose (mcg/min)||Continuous Infusion Rate (mL/hr)|
|NOTE: 1 mg = 1000 mcg; 1 kg =
† Additional intravenous bolus dose of 150 mcg/kg should be administered if ACT less than 300 seconds.
* No bolus dose is given if ACT greater than 450 seconds
For use in PCI, therapy with Argatroban Injection is monitored using ACT. Obtain ACTs before dosing, 5 to 10 minutes after bolus dosing, following adjustments in the infusion rate, and at the end of the PCI procedure. Obtain additional ACTs every 20 to 30 minutes during a prolonged procedure.
Continued Anticoagulation after PCI
If a patient requires anticoagulation after the procedure, Argatroban Injection may be continued, but at a rate of 2 mcg/kg/min and adjusted as needed to maintain the aPTT in the desired range [see Dosing in Patients with Heparin-Induced Thrombocytopenia].
Dosing In Patients With Hepatic Impairment
For adult patients with HIT and moderate or severe hepatic impairment (based on Child-Pugh classification), an initial dose of 0.5 mcg/kg/min is recommended, based on the approximately 4-fold decrease in argatroban clearance relative to those with normal hepatic function. Monitor the aPTT closely, and adjust the dosage as clinically indicated.
Achievement of steady-state aPTT levels may take longer and require more dose adjustments in patients with hepatic impairment compared to patients with normal hepatic function.
For patients with hepatic impairment undergoing PCI and who have HIT or are at risk for HIT, carefully titrate Argatroban Injection until the desired level of anticoagulation is achieved. Use of Argatroban Injection in PCI patients with clinically significant hepatic disease or AST/ALT levels greater than or equal to 3 times the upper limit of normal should be avoided [see WARNINGS AND PRECAUTIONS].
Dosing In Pediatric Patients With Heparin-Induced Thrombocytopenia/Heparin-Induced Thrombocytopenia And Thrombosis Syndrome
Initial argatroban infusion doses are lower for seriously ill pediatric patients compared to adults with normal hepatic function [see Use in Specific Populations].
In general, therapy with argatroban is monitored using the aPTT. Tests of anticoagulant effects (including the aPTT) typically attain steady-state levels within one to three hours following initiation of argatroban in patients without hepatic impairment [see WARNINGS AND PRECAUTIONS] . Dose adjustment may be required to attain the target aPTT. Check the aPTT two hours after initiation of therapy and after any dose change to confirm that the patient has attained the desired therapeutic range.
Dosage Adjustment: [see Use in Specific Populations]
Conversion To Oral Anticoagulant Therapy
Initiating Oral Anticoagulant Therapy
When converting patients from argatroban to oral anticoagulant therapy, consider the potential for combined effects on International Normalized Ratio (INR). To avoid prothrombotic effects and to ensure continuous anticoagulation when initiating warfarin, overlap Argatroban Injection and warfarin therapy. There are insufficient data available to recommend the duration of the overlap. Initiate therapy using the expected daily dose of warfarin. A loading dose of warfarin should not be used.
The relationship between INR and bleeding risk is altered when argatroban and warfarin are coadministered. The combination of argatroban and warfarin does not cause further reduction in the vitamin K–dependent factor Xa activity than that which is seen with warfarin alone. The relationship between INR obtained on combined therapy and INR obtained on warfarin alone is dependent on both the dose of argatroban and the thromboplastin reagent used. The INR value on warfarin alone (INRW) can be calculated from the INR value on combination argatroban and warfarin therapy [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY] .
Coadministration of Warfarin and Argatroban Injection at Doses Up to 2 mcg/kg/min
Measure INR daily while Argatroban Injection and warfarin are coadministered. In general, with doses of Argatroban Injection up to 2 mcg/kg/min, Argatroban Injection can be discontinued when the INR is greater than 4 on combined therapy. After Argatroban Injection is discontinued, repeat the INR measurement in 4 to 6 hours. If the repeat INR is below the desired therapeutic range, resume the infusion of Argatroban Injection and repeat the procedure daily until the desired therapeutic range on warfarin alone is reached.
Coadministration of Warfarin and Argatroban Injection at Doses Greater than 2 mcg/kg/min
For doses greater than 2 mcg/kg/min, the relationship of INR between warfarin alone to the INR on warfarin plus argatroban is less predictable. In this case, in order to predict the INR on warfarin alone, temporarily reduce the dose of Argatroban Injection to a dose of 2 mcg/kg/min. Repeat the INR on Argatroban Injection and warfarin 4 to 6 hours after reduction of the Argatroban Injection dose and follow the process outlined above for administering Argatroban Injection at doses up to 2 mcg/kg/min.
Dosage Forms And Strengths
Argatroban Injection is supplied in a single use polyolefin bag containing 250 mg argatroban in 250 mL aqueous sodium chloride solution (1 mg/mL). The solution is ready for intravenous infusion.
Storage And Handling
Argatroban Injection is supplied as a single use polyolefin bag containing 250 mg argatroban in 250 mL of aqueous sodium chloride solution (1 mg/mL). The polyolefin bag has a single port which is sealed with a rubber stopper and flip-off seal, and is stored in an aluminum foil overpouch with clear window.
NDC 0703-0020-32 one carton containing 5 polyolefin bags of Argatroban Injection (each bag contains 250 mg of argatroban).
Store the bag in its original carton at 20° to 25° C (68° to 77°F) (see USP Controlled Room Temperature). Do not freeze. Retain in the original carton to protect from light.
Manufactured In Hungary By: Teva Pharmaceutical Works Ltd. Hungary, H-2100 Godollo Tancsics M. ut 82 Hungary. Manufactured For: Teva Pharmaceuticals USA, Sellersville, PA 18960. Issued. 11/2014
Last reviewed on RxList: 12/30/2014
This monograph has been modified to include the generic and brand name in many instances.
Additional Argatroban Information
Argatroban - User Reviews
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